(P 432) EXPANSION OF A PHASE 1 STUDY OF SON-1010 (IL12-FHAB) ADDING TRABECTEDIN IN SOFT TISSUE SARCOMA: TRIAL IN PROGRESS

Objective: Interleukins have had limited success due to inefficient tumor targeting and short pharmacokinetics (PK), requiring frequent dosing leading to aberrant immunostimulation and toxicity. IL-12 potently activates NK, NKT, Th1, and cytotoxic CD8 T cells to produce IFN-gamma and efficiently kill tumor cells in mice, yet clinical studies of recombinant IL-12 at the maximum tolerated dose (MTD) of 500 ng/kg have failed to show adequate therapeutic benefit in humans. A novel platform technology was developed that delivers cytokine(s) linked to a fully-human albumin binding (FHAB®) scFv domain. Single-chain native IL 12 linked to the FHAB (SON-1010) provides enhanced targeting and retention through albumin binding to over-expressed FcRn, GP60, and SPARC in the tumor microenvironment (TME), with an improved PK profile, a dose-sparing effect that decreases the toxicity risk, and a broader therapeutic index. The safety of SON-1010 along with its PK and PD is being studied clinically as monotherapy (study SB101) in advanced solid tumors and the target MTD of 1200 ng/kg was recently achieved. Trabectedin (Yondelis®) is licensed for patients with metastatic soft tissue sarcoma (STS). While trabectedin is an alkylating drug, it also activates tumor macrophages toward a pro-inflammatory phenotype. SON-1010 may ‘warm up’ the TME to improve the effectiveness of trabectedin in these immunologically-active tumors.

Methods: SB101 is a Phase 1 dose-escalation study that assessed the safety, tolerability, PK, PD, and efficacy of SON-1010 dosed every 3 weeks to establish the MTD (NCT05352750). An expansion cohort adding alternating doses of trabectedin in 18 patients with STS was designed to show added benefit using a Simon 2-stage statistical approach. Enrollment of the expansion cohort is in progress and follow-up is ongoing. The combination of SON-1010 with trabectedin offers a unique opportunity to use this extended half-life version of IL-12 to augment the potential for tumor control in STS, which represents a significant unmet medical need.

Results: N/A

Conclusion: N/A